University of North Carolina at Chapel Hill chemists have developed what they believe is a breakthrough method of creating the world’s tiniest manufactured particles for delivering drugs and other organic materials into the human body.

Adapting technology pioneered by the electronics industry in fabricating transistors, the team has figured out for the first time how to create particles for carrying genetic material, pharmaceuticals and other compounds of unprecedented small size and uniformity. The tiny bits are so small they can be designed and constructed to measure only a hundred nanometers or so in diameter. A nanometer is a billionth of a meter.

Leading the group is Dr. Joseph M. DeSimone, William R. Kenan Jr. Distinguished professor of chemistry and chemical engineering at UNC and N.C. State University. A member of the UNC College of Arts and Sciences and the National Academy of Engineering, DeSimone also directs the National Science Foundation Science and Technology Center for Environmentally Responsible Solvents and Processes and the Institute for Advanced Materials, Nanoscience and Technology at UNC.

"Billions of dollars are being spent now on nanotechnology and nanoparticles, but 99 percent of the materials people are focusing on are metals and metal oxides, which are inorganic," DeSimone said. "Our method, which is really exciting, for the first time opens the world’s door to marrying organic materials to nanotechnology. Biology, after all, is almost exclusively organic materials.

"We really believe this work will have a profound positive impact down the road on human health care. This includes, but is not limited to, chemotherapy, gene therapy, disease detection and drug delivery."

A report on the findings appeared online this morning (June 21) in the Journal of the American Chemical Society. Other authors -- all in chemistry at UNC -- are Drs. Jason P. Rolland and Ginger M. Denison, recent Ph.D. recipients; Drs. Benjamin W. Maynor and Larkin E. Euliss, postdoctoral fellows; and graduate student Ansley E. Exner.

Until now, DeSimone said, most current techniques for particle formation were incompatible with organic materials. That was because they involved baking, etching or processing robust metals and such with solvents that would have destroyed far more fragile organic matter such as genes or drugs.

The new method avoids harsh treatment but also allows formation of uniform particles in any shape designers choose – spheres, rods, cones, trapezoidal solids, etc. -- and essentially any composition, he said. The relatively simple process, which he and colleagues are calling Particle Replication in Nonwetting Templates, or PRINT, also avoids creating films or "scum layers" that would clump particles together rather than allowing them to be harvested independent of one another.

"This is in contrast to traditional imprint lithography with silicon, glass or quartz molds where it is difficult to eliminate this residual material between objects," DeSimone said.

Particles injected into the body can be designed to be biodegradable, he said. Some are made from the same material used to make surgical sutures. They will incorporate as "cargo" whatever biological material designers want to get into patients’ bloodstreams for more efficient uptake by cells for diagnostic testing or therapy.

Studies with various organic compounds have been very successful, the chemist said. New studies with mice have recently begun at the UNC School of Medicine, which DeSimone joined as professor of pharmacology.

"The process starts off when we make a master template in a clean room at places like the Triangle National Lithography Center at N.C. State University," DeSimone said. "From that we make impressions with what we call liquid Teflon, and the resulting molds look something like ice cube trays with tiny cavities in them. After that, we mold the carrier and fragile functional materials into whatever particles we want and gently wash them off the molds with buffer solutions into vials or other containers to concentrate them. Then they can be injected."

DeSimone, his colleagues, UNC and others have formed a new company, Liquidia Technologies Inc., with $2.5 million in angel funding and venture capital to further develop and commercialize the unique new technology. It is the second company for which DeSimone has been largely responsible.

The first was MiCell Technologies, which developed his research showing that it was possible to use carbon dioxide as a solvent in place of organic solvents, which polluted the environment.

"We are most excited about the commercial implications of Professor DeSimone’s breakthrough with PRINT," said Dr. Lowry Caudill, chairman of Liquidia. "We believe that the PRINT process is an extremely versatile method that offers unparalleled uniformity and precision for making organic nanoparticles that will have profound implications in medicine and many other industries, including display technologies.

"Prior to this, no one else has fused the highly uniform and precise methods for fabricating transistors with the organic nanoparticle world," said Bruce Boucher, president of Liquidia. "It is truly a revolutionary discovery."

Support for the research came from the Office of Naval Research, the National Science Foundation and the William R. Kenan Jr. Distinguished Professorship.

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